Compositions capable of strengthening epidermal tight junctions to prevent and / or treat atopic dermatitis

Abstract

The present invention relates to a composition beneficial for cosmetics, comprising: - at least one basic amino acid chosen from arginine, lysine, histidine, ornithine, hydroxyproline and one of their salts; and - at least one glycosylceramide, and its use for the prevention and / or treatment of atopic dermatitis.

Description

Technical Field

[0001] This invention relates to the field of skin care, and more specifically, to the treatment of inflammatory skin diseases. More precisely, this invention relates to a composition for the prevention and / or treatment of atopic dermatitis, preferably a cosmetic. Background Technology

[0002] Atopic dermatitis, or atopic eczema, is a pruritic, chronic inflammatory dermatitis—an inflammatory skin condition characterized by intense and chronic itching and recurrent, sporadic eczematous lesions (Mack and Kim, 2018; Weidinger et al., 2018). This condition is associated with impaired skin barrier function or, in fact, with the possible occurrence of other symptoms, such as allergic rhinitis, asthma, or allergies to environmental allergens that are normally tolerable in healthy subjects.

[0003] Changes in the epidermal barrier function play a crucial role in the development of atopic dermatitis (Kuo et al., 2013). In fact, a lack of epidermal barrier function leads to a vicious cycle of itching and scratching (Mochizuki et al., 2019), which increases the permeability of allergens, bacteria, and viruses (Cipriani et al., 2014; Halling-Overgaard et al., 2017), which in turn acts as a mediator in the process of increased inflammation.

[0004] Tight junctions (or occluded bands) are intercellular connections essential for epithelial adhesion (or intercellular adhesion) and barrier function. They are dynamic transmembrane complexes that can open and close. These tight junctions consist of structural proteins, cytoskeleton-associated proteins, and proteins involved in signal transduction and cell polarity mechanisms (Niessen, 2007).

[0005] Specifically, tight junctions are composed of transmembrane proteins such as closure proteins, latching proteins, junctional adhesion molecules (JAMs), and tricellular tight junction proteins, which are structural proteins similar to latching proteins; and cytoplasmic proteins such as closure band (ZO) proteins, cingulins, multi-PDZ domain protein 1 (MUPP1) proteins, or actually membrane-associated guanylate kinase (MAGI) proteins with an inverted orientation.

[0006] Tight junctions are found, in particular, in the granular layer (or granular layer) of the epidermis (Brandner et al., 2002).

[0007] The primary function of tight junctions in the skin is to establish a second skin barrier, which intervenes immediately when the stratum corneum (or stratum corneum) of the epidermis is broken.

[0008] Several scientific studies have shown that the expression of several proteins that make up tight junctions is altered in the skin of patients with atopic dermatitis; in particular, the expression of claudin-1 is significantly reduced in the lesion area of ​​patients with atopic dermatitis (Batista et al., 2015; Gruber et al., 2015).

[0009] The foregoing indicates that restoring the expression and function of tight junctions provides a novel approach to strengthening or rebuilding the skin barrier function, and therefore, for the prevention and / or treatment of atopic dermatitis.

[0010] For example, documents EP 2 691 090 and EP 2 704 704 describe the use of cosmetic active ingredients (plant polyphenols, flavonoids or cisuric acid) and probiotics, respectively, in strengthening tight bonds for the purpose of treating atopic dermatitis.

[0011] However, the solutions proposed in these documents correspond to undefined compositions of plant extracts and bacterial lysates that may cause allergic or inflammatory reactions when applied to human skin, and in which the compositions may vary significantly between batches.

[0012] Therefore, there is a clear need to develop a composition containing pure skin-active compounds that help restore the function of tight junctions in pre- and atopic skin, and also have high titers of active molecules that would lead to the prevention and / or treatment of atopic dermatitis, particularly for long-term use, and be safe for topical human use, i.e., fully compatible with the skin, and ideally biomimetic, i.e., identical in composition to human skin. Summary of the Invention

[0013] The applicant has demonstrated that, surprisingly, several skin-active ingredients that are completely safe and suitable for use in human cosmetics can overcome the aforementioned drawbacks and meet the aforementioned needs.

[0014] Generally speaking, the purpose of this invention is to respond to real needs, especially cosmetic needs, while moisturizing and soothing the skin, reducing discomfort, and ultimately improving the appearance of the skin.

[0015] In particular, the present invention aims to treat atopic dermatitis to improve skin appearance and reduce imperfections.

[0016] More precisely, the applicant has demonstrated that the compounds or active ingredients contained in the compositions of the present invention act synergistically to induce the expression of claudin-1 (a key structural protein in tight junctions). These fully biomimetic compounds can be used to formulate skin cosmetic products suitable for the prevention and / or treatment of atopic dermatitis.

[0017] In the context of this invention, the term "active ingredient" refers to a substance or compound having biological and / or therapeutic properties and having physiological effects.

[0018] The active ingredient is different from at least one excipient present in the composition of the present invention.

[0019] The term "excipient" refers to a substance other than the active ingredient that provides the composition with properties of the active ingredient, particularly viscosity, Galen properties, and / or vectorization properties.

[0020] In the context of this invention, the term "biomimetic compound" refers to a compound that is naturally present on / inside healthy skin and its appendages, or that, upon hydrolysis or oxidation / reduction, is transformed into a compound that is also naturally present on / inside healthy skin and its appendages. According to this invention, the compound is considered to be in a separated state, in a form identical to its natural form, or modified compared to its natural form, but retaining cellular compatibility with the skin regardless of how it is obtained or produced.

[0021] Therefore, according to a first aspect, the present invention relates to a composition comprising:

[0022] - At least one basic amino acid, preferably selected from the group consisting of arginine, lysine, histidine, ornithine, and hydroxyproline; and

[0023] - At least one glycosylceramide.

[0024] According to specific embodiments, the compositions of the present invention are cosmetic or skin pharmaceutical compositions, preferably cosmetics.

[0025] Amino acids are fully biomimetic active ingredients because they exist in all living organisms, whether as protein components or in free form after degradation.

[0026] In the context of this invention, the term "basic amino acid" means any form of amino acid, including any salt.

[0027] Glycosylceramides are glycolipids composed of ceramide bonds linked by β-glycosidic bonds to a single neutral ose (monosylceramide) or multiple neutral oses (polysylceramide), wherein the ceramide is an amide of sphingosine and a fatty acid. Preferably, the neutral sugar is a hexose or deoxyhexose selected from the group consisting of allose, arbutin, glucose, mannose, gulose, idole, galactose, fucose, and fructose. The fatty acid preferably has a long chain and typically contains 16 to 18 carbon atoms, which is optionally hydroxylated. Preferably, the ceramide is selected from the group consisting of ceramide-1, ceramide-2, ceramide-3, ceramide-4, ceramide-5, ceramide-6, and ceramide-7.

[0028] Glycosylceramides are present in all living organisms, especially humans, where they are particularly abundant in nerve and brain tissue as myelin components. Therefore, glycosylceramides are considered biomimetic compounds.

[0029] According to a specific embodiment, the basic amino acid contained in the composition of the invention is arginine or one of its salts.

[0030] Arginine is typically found in various forms, including D-arginine, D,L-arginine, and L-arginine. Examples of organic or inorganic salts of arginine that may be mentioned include hydrochloride, glutamate, butyrate, and glycolate.

[0031] Preferably, the composition of the present invention contains L-arginine.

[0032] According to one specific embodiment, the arginine used in the compositions of the present invention is in a purified form, preferably with a purity of at least 60%, more preferably at least 70%, advantageously at least 80%, even more advantageously at least 90%, or even at least 95% or even 98%. The arginine contained in the compositions of the present invention can be derived from plant or chemical sources, or actually obtained through biotechnology. Therefore, L-arginine, a cosmetic raw material with the INCI name arginine, sold by Kyowa Hakko Co., Ltd. of Japan, can be used in the compositions of the present invention.

[0033] According to a particular embodiment, the compositions of the present invention comprise at least one monosaccharide ceramide and / or a polysaccharide ceramide form of glycosaccharide ceramide, advantageously monosaccharide ceramide and / or tetrasaccharide ceramide.

[0034] According to a preferred embodiment, the composition of the present invention comprises monosaccharide ceramide and glycosaccharide ceramide in the form of tetrasaccharide ceramide.

[0035] According to one particular embodiment, the composition comprises a monosaccharide ceramide corresponding to glucuronic acid (or gluconate) covalently bound to ceramide via a β-glycosidic bond.

[0036] According to a particular embodiment, the polysaccharide-based ceramide of the present invention corresponds to an oligosaccharide covalently bonded to ceramide via a β-glycosidic bond.

[0037] Advantageously, the polysaccharide ceramide of the present invention is a tetrasaccharide ceramide, the oligosaccharide of which corresponds to the following sugar in series: glucuronic acid-glucanonic acid-galactose-mannose (or GlcA-GlcN-Gal-Man).

[0038] According to a particular embodiment, the glycosylceramide or plurality of glycosylceramides of the present invention are in a purified form with a purity of at least 60%, preferably at least 70%, advantageously at least 80%, even more advantageously at least 90%, or even at least 95%.

[0039] The glycosylceramides or multiple glycosylceramides contained in the compositions of the present invention may be of plant origin or actually obtained by biotechnology.

[0040] Advantageously, the compositions of the present invention comprise at least one biotechnologically derived glycosylceramide.

[0041] Advantageously, all glycosylceramides contained in the compositions of the present invention are of biotechnology origin.

[0042] According to a particular embodiment, the glycosylceramides of the present invention are of biotechnological origin, particularly obtained by extraction from the membranes of bacterial species (e.g., *Pseudomonas*). Advantageously, glucosylceramides are obtained from the bacterial species *Pseudomonas paucimobilis*. Therefore, cosmetic raw materials glycosphingolipids and biosphingoliposides, marketed by THREE B CO., INC. and KIKKOMAN BIOCHEMIFA COMPANY respectively and bearing the INCI name glycosphingolipid, can be used in the compositions of the present invention.

[0043] According to a particular embodiment, at least one basic amino acid, advantageously arginine or a salt thereof, accounts for 0.001% to 2% of the total weight of the composition, advantageously 0.01% to 0.5%.

[0044] According to another specific embodiment, at least one glycosylceramide, advantageously in the form of monosaccharide ceramide and tetrasaccharide ceramide, accounts for 0.0001% to 1% of the total weight of the composition, advantageously 0.001% to 0.1%.

[0045] In one particular embodiment, the composition of the present invention further comprises at least one triterpene saponoside or a derivative thereof, selected from the group consisting of glycyrrhetinic acid, glycyrrhizin, stearyl glycyrrhetinic acid ester and dipotassium diglycyrrizinate.

[0046] These compounds derived from licorice have anti-inflammatory properties and are commonly used topically to treat atopic dermatitis to combat the itching associated with this skin condition. For example, cosmetic starting materials 18β-glycyrrhetinic acid, dipotassium glycyrrhizate, and glycyrrhizic acid, corresponding to the INCI names glycyrrhetinic acid, dipotassium glycyrrhizate, and glycyrrhizic acid and stearyl glycyrrhetinic acid ester (all named according to their INCI names and available from the listed manufacturers, e.g., those listed in the INCI International Buyer's Guide), can be used in the compositions of this invention.

[0047] Advantageously, in addition to basic amino acids and at least one glycosylceramide, the compositions of the present invention comprise a combination of glycyrrhetinic acid and dipotassium diglycyrrhizate, which have anti-inflammatory capabilities.

[0048] According to a particular embodiment, at least one of the triterpenoid saponins or their derivatives accounts for between 0.0001% and 10% of the total weight of the composition, advantageously between 0.01% and 5%, and preferably between 0.05% and 1%.

[0049] According to one embodiment, the composition of the present invention further comprises at least one nonionic surfactant selected from sucrose esters and / or sorbitol esters.

[0050] According to one specific embodiment, at least one nonionic surfactant of the present invention accounts for 0.1% to 5% of the total weight of the composition, advantageously 1% to 3%.

[0051] Suitable sucrose esters and / or sorbitan esters used in this invention are described in detail in document WO 2014 / 023895, which is incorporated herein by reference in its entirety. These agents, used alone or in combination, can be used to reduce the adhesion and / or proliferation of Staphylococcus aureus on the skin and / or nasal mucosa, subsequently improving the general clinical condition of atopic dermatitis.

[0052] According to a preferred embodiment, the nonionic surfactant of the present invention corresponding to dehydrated sorbitan ester is polysorbate 20 (INCI) or polysorbate 80 (INCI), advantageously polysorbate 20.

[0053] According to another preferred embodiment, the nonionic surfactant of the present invention corresponding to sucrose ester is a sucrose stearate having a hydrophilic-lipophilic balance (HLB) value of at least 16, which corresponds to the sucrose monoester and stearic acid being contained in a relative ratio of 75% and 80% by weight of sucrose stearate (INCI).

[0054] According to one particular embodiment, the nonionic surfactant of the present invention accounts for 0.1% to 5% of the weight of the composition, advantageously between 1% and 3%.

[0055] According to one particular embodiment, the compositions of the present invention further comprise at least one lipid capable of restoring the skin barrier, advantageously selected from the group consisting of:

[0056] - At least one exogenous lipid for the skin, preferably a plant oil;

[0057] - A mixture of naturally occurring ingredients in the skin, including ceramide-1, ceramide-3, ceramide-6; cholesterol; free fatty acids and phytosphingosine; and

[0058] - Squalane.

[0059] In one particular implementation, the skin exogenous lipids correspond to sunflower seed oil (INCI: sunflower seed oil), rapeseed oil (INCI: rapeseed oil), and / or jojoba oil (INCI: jojoba oil). Simmondsia chinensis (Jojoba) seed oil). These three plant oils have known moisturizing and anti-inflammatory properties.

[0060] In one particular embodiment, the mixture of ingredients naturally present in the skin is in the form of a composition comprising lipids having the following INCI names: sodium lauroyl lactylate, ceramide NP, ceramide AP, phytosphingosine, cholesterol, and ceramide EOP.

[0061] In one particular embodiment, the lipid capable of restoring the skin barrier is squalane, a lipid also present in skin compositions. In the context of this invention, squalane is advantageously of plant origin.

[0062] Preferably, the lipids capable of restoring the skin barrier account for between 0.01% and 25% of the weight of the composition, advantageously between 1% and 15%.

[0063] According to one particular embodiment, the compositions of the present invention further comprise at least one additional polyhydroxy compound selected from rhamnose, xylitol, and mannitol. These polyhydroxy compounds help reduce the adhesion of pathogenic bacteria such as Staphylococcus aureus to human skin and mucous membranes (including nasal mucosa). Mannitol has free radical scavenging activity.

[0064] In a particular embodiment of the invention, the composition comprises a mixture of the three additional polyhydroxy compounds described above. Advantageously, rhamnose accounts for 0.01% to 1% of the total weight of the composition, xylitol accounts for 0.05% to 2% of the total weight of the composition, and mannitol accounts for 0.005% to 1% of the total weight of the composition.

[0065] Advantageously, the compositions of the present invention further comprise vitamin PP, also known as vitamin B3, nicotinamide, or nicotinamide, or one of its derivatives; these compounds are known to stimulate the synthesis of lipids in the stratum corneum, such as ceramides, free fatty acids, and cholesterol. The role of vitamin PP is to activate the activity of serine palmitoyltransferase, a key enzyme in the synthesis of sphingosine (a precursor molecule of ceramides).

[0066] According to a particular embodiment, one of nicotinamide and / or its derivatives accounts for between 0.001% and 10% of the total weight of the composition, advantageously between 0.01% and 5%, and preferably between 0.1% and 2%.

[0067] According to a particular embodiment, the compositions of the present invention comprise prebiotic substances, particularly oligosaccharides such as fructooligosaccharides or FOS (INCI), short-chain dextrins (INCI), arabinogalactan (INCI), inulin (INCI), or lactulose (INCI). In a preferred embodiment, the compositions of the present invention comprise FOS, namely oligosaccharides of fructose and sucrose with a degree of polymerization of 2 to 10. FOS helps induce β-defensins and is also metabolized by saprophytic flora. FOS has antimicrobial properties and can be used to reduce the use of artificial preservatives, as described in document FR 2 831 059.

[0068] Advantageously, the FOS content is between 0.001% and 20% of the total weight of the composition, advantageously between 0.01% and 10%, and preferably between 0.1% and 5%.

[0069] According to certain embodiments, the compositions of the present invention further comprise at least one antimicrobial peptide inducer, i.e., capable of inducing the synthesis and / or secretion of human or microbial antimicrobial peptides (especially β-defensins). These properties are particularly evident in plant extracts, such as extracts from boldo or meadowsweet.

[0070] Advantageously, the antimicrobial peptide inducer is Bordeaux tree extract, meadowsweet extract, or a mixture thereof.

[0071] According to one particular embodiment, the antimicrobial peptide inducer accounts for 0.001% to 5% of the total weight of the composition, preferably 0.01% to 1%.

[0072] According to certain embodiments, the compositions of the present invention are in a cosmetically and / or skin-acceptable form, i.e., compatible with skin, mucous membranes, hair, nails and / or scalp.

[0073] According to a preferred embodiment, the composition of the present invention is in a form suitable for local administration.

[0074] In another embodiment, the advantageous cosmetic composition of the present invention further comprises a bioactive system that, on the one hand, binds in an aqueous solution a stable form of a nucleotide selected from ATP (adenosine triphosphate), Gp4G (guanosine tetraphosphate), and Ap4A (adenosine tetraphosphate); and on the other hand, at least one biomimetic peptide comprising up to six amino acids, advantageously different from those of the present invention, mimicking skin polypeptides or skin proteins, or agonist or antagonist biomolecules of said peptides or proteins. In practice, the combination of these active ingredients means that, due to the use of biomimetic peptides, the metabolic activity of skin cells can be catalyzed while achieving cosmetic or therapeutic effects on the skin. These latter can be selected to obtain desired effects, such as inhibitory effects on neurogenic stimulation, depigmentation activity, inhibition of any intolerance or sensitization, etc.

[0075] In fact, in the bioactive system of the present invention, nucleotides account for up to 10% of the total weight of the composition, preferably between 0.001% and 5%; and biomimetic peptides account for 0.001% to 1% of the total weight of the composition.

[0076] According to another embodiment, the compositions of the present invention may additionally comprise extracts from Arthrobacter, particularly carotenoid-rich extracts (INCI: micrococcal lysate). Advantageously, the compositions of the present invention comprise this type of dry extract, comprising 0.00001% to 0.1% of the total weight of the composition, preferably 0.0001% to 0.001%.

[0077] According to another embodiment, the composition of the present invention further includes other components that contribute to internal protection through their effects of protecting DNA, reducing UV radiation-induced immunosuppression, free radical scavenging, or a combination of these effects.

[0078] If the formulation of the present invention further comprises one or more antioxidants, the protective effect of the formulation against oxidative stress or against free radical activity can be further enhanced. Those skilled in the art will readily select the antioxidants from starting materials used in the cosmetic field.

[0079] In a specific embodiment of the invention, the composition further comprises an active ingredient capable of stimulating skin cell proliferation, advantageously fibroblasts and / or keratinocytes, preferably human or animal fibroblasts. In particular, and according to this embodiment, the composition further comprises:

[0080] - α-Lipoic acid or one of its salts;

[0081] - A vitamin C derivative selected from ethyl ascorbate and sodium ascorbate, or a mixture thereof; and

[0082] - Hyaluronic acid, the molecular weight (Mw) of which is advantageously contained between 0.5 and 15 kDa, preferably between 0.5 and 10 kDa.

[0083] Advantageously, one of the α-lipoic acid or its salts accounts for less than 0.1% of the total weight of the composition, advantageously less than 0.01%, preferably between 0.001% and 0.0005%.

[0084] Advantageously, a vitamin C derivative selected from ethyl ascorbate and sodium ascorbate or mixtures thereof, preferably ethyl ascorbate, preferably 3-O-ethyl ascorbate ether, accounts for 0.001% to 10% of the total weight of the composition, advantageously 0.01% and 5%, preferably between 0.1% and 1%.

[0085] Advantageously, the hyaluronic acid, having a molecular weight (Mw) between 0.5 and 15 kDa, preferably between 0.5 and 10 kDa, accounts for between 0.001% and 10% of the total weight of the composition, advantageously between 0.01% and 5%, preferably between 0.1% and 1%.

[0086] According to another embodiment of the invention, the composition further comprises at least one or even all of the following components, which exert in vivo biological effects on cells of skin, lips, hair, and / or mucous membranes exposed to UV-A and / or UV-B radiation:

[0087] - Free radical scavengers that protect cell structure, such as vitamin E and / or its fat-soluble or water-soluble derivatives, particularly tocotrienols and / or tocopherols, advantageously constitute 0.001% to 10% of the total weight of the composition, even more advantageously between 0.02% and 2%, preferably 0.04%;

[0088] - Restrictive immunosuppressive agents, such as vitamin PP, advantageously constitute between 0.001% and 1% of the total weight of the composition, preferably between 0.01% and 0.3%;

[0089] - A protective agent for the p53 protein, such as epigallocatechin gallate (EGCG), advantageously accounts for 0.001% to 0.1% of the total weight of the composition, preferably 0.005% to 0.05%.

[0090] The compositions of the present invention may also additionally contain peptide extracts of soybean and / or wheat.

[0091] In practice, peptide extracts derived from soybean or wheat grains are obtained by enzymatic hydrolysis of the grains using peptidases and can be used to recover peptides with an average size of 700 Da. Preferably, the soybean peptide extract is the extract identified by CAS number 68607-88-5 and / or the wheat peptide extract is the extract identified by CAS number 70084-87-6. The wheat and soybean extracts can correspond to the INCI names hydrolyzed wheat protein and hydrolyzed soybean protein, respectively.

[0092] In one particular embodiment, soybean and wheat peptide extracts are used together, for example, in weight ratios between 80 / 20 and 20 / 80, advantageously between 70 / 30 and 30 / 70, preferably equal to 60 / 40.

[0093] In an advantageous embodiment, the soybean and / or wheat peptide extract is free of synthetic GHK tripeptide (glycyl-histyl-lysine; INCI: tripeptide-1). In practice, the soybean and / or wheat peptide extract constitutes between 0.01% and 20% of the total weight of the composition, advantageously between 0.1% and 10%, and preferably between 0.2% and 0.7%.

[0094] According to alternative embodiments and advantageously, the compositions of the present invention further comprise at least one ultraviolet absorber. It is well known that filtering ultraviolet light can improve the skin condition of patients with atopic dermatitis.

[0095] In the context of this invention, the term "ultraviolet absorber" includes organic or inorganic compounds capable of filtering UV-A, UV-B, and / or UV-C.

[0096] According to the present invention, these may also be inorganic absorbents instead of chemical or organic absorbents.

[0097] The compositions of the present invention may contain one or more broad-spectrum ultraviolet absorbers, namely compounds or mixtures that absorb UV-A, UV-B, UV-C and possibly visible light.

[0098] Examples of broad-spectrum organic absorbents that can be used in the context of this invention are absorbents corresponding to the following INCI names: terphenyltriazine, bisethylhexyloxyphenol methoxyphenyltriazine, and methylene bis-benzotriazolyltetramethylbutylphenol. Another example of a broad-spectrum absorbent suitable for the compositions of this invention has the INCI name diethylhexylbutyrylaminotriazine.

[0099] Therefore, in one particular embodiment, the composition of the present invention comprises at least one absorbent selected from the following compounds, identified by their INCI names: terphenyltriazine, bisethylhexyloxyphenol methoxyphenyltriazine, and methylene bis-benzotriazolyltetramethylbutylphenol, diethylhexylbutyramide triazine, or mixtures thereof.

[0100] Advantageously, the composition comprises a filter bis-ethylhexyloxyphenol methoxyphenyl triazine.

[0101] According to another embodiment, instead of a broad-spectrum absorber or in addition to a broad-spectrum absorber, the composition contains at least one organic and / or inorganic UV-A and / or UV-B absorber, which may be in an aqueous (lipophilic) and / or oil (lipophilic) phase.

[0102] Therefore, for example, the compositions of the present invention may contain a lipid-soluble UV-B absorber that can help stabilize or solubilize the broad-spectrum absorbers, or actually stabilize them, and thus increase the sun protection factor (SPF).

[0103] Advantageously, this type of absorbent corresponds to the following INCI names: homosalate, octocrylene, ethylhexyl salicylate, and ethylhexyl triazine.

[0104] In a preferred embodiment, the composition of the present invention comprises ethylhexyltriazine ketone.

[0105] In another embodiment, the lipid-soluble UV-B absorber is α-(trimethylsilyl)-ω-(trimethylsiloxy)poly[oxy(dimethyl)methylenesilyl]-co-[oxy(methyl)(2-{4-[2,2-bis(ethoxycarbonyl)vinyl]phenoxy}-1-methyleneethyl)methylenesilyl]-co-[oxy(methyl)(2-(4-[2,2-bis(ethoxycarbonyl)vinyl]phenoxy)prop-1-enyl)methylenesilyl], an organosilicon polymer (INCI: polysilicone-15) capable of filtering UV-B.

[0106] In a preferred embodiment, the composition of the present invention comprises at least one UV-B absorber selected from compounds of the group consisting of, identified by their INCI names: homosalate, ethylhexyl salicylate, ethylhexyl triazine ketone, polysiloxane-15, or mixtures thereof.

[0107] In one particular embodiment, the composition does not contain the following filters: 4-methylbenzyl camphor, benzophenone-2, benzophenone-3, ethylhexyl methoxycinnamate, and octocrylene.

[0108] In one advantageous embodiment, the composition of the present invention comprises at least one UV-A absorber to ensure complete filtration of the harmful portions of the solar spectrum.

[0109] In the context of this invention, advantageous UV-A absorbers are butyl methoxydibenzoylmethane (INCI) and diethylaminohydroxybenzoylhexyl benzoate (INCI).

[0110] In one specific embodiment, the UV-A absorber is bis-(diethylaminohydroxybenzoylbenzoyl)piperazine (INCI) (CAS No. 919803-06-8).

[0111] Therefore, in a preferred embodiment, the composition of the present invention comprises an absorbent of at least one compound selected from the group consisting of compounds identified by their INCI names: butyl methoxydibenzoylmethane, hexyl diethylaminohydroxybenzoylbenzoate, bis-(diethylaminohydroxybenzoylbenzoyl)piperazine, or mixtures thereof.

[0112] Other advantageous ultraviolet absorbers in the context of this invention are water-soluble absorbers, such as:

[0113] - An absorbent corresponding to the INCI name disodium phenyldibenzimidazole tetrasulfonate;

[0114] - Absorbent corresponding to the INCI name phenylbenzimidazole sulfonic acid.

[0115] In a preferred embodiment, the composition of the present invention comprises at least one water-soluble absorbent selected from the group consisting of compounds identified by their INCI names: disodium phenyl dibenzimidazole tetrasulfonate, phenyl benzimidazole sulfonic acid, or mixtures thereof.

[0116] Advantageously, inorganic mineral filters or mineral screens are metal oxides and / or other compounds that are difficult to dissolve or insoluble in water, particularly oxides of the following substances: titanium (TiO2), zinc (ZnO), iron (Fe2O3), zirconium (ZrO2), silicon (SiO2), manganese (e.g., MnO), aluminum (Al2O3), or cerium (Ce2O3).

[0117] According to one particular embodiment, inorganic mineral sieves can be used in the form of commercially available oily or aqueous predispersants. These predispersants can advantageously be supplemented with dispersing agents and / or solubilizing media.

[0118] Inorganic mineral filters can also be surface-treated or encapsulated to give them hydrophilic, amphiphilic, or hydrophobic properties. Such surface treatments may include providing the mineral sieve with inorganic and / or organic, hydrophilic and / or hydrophobic films.

[0119] In a preferred embodiment, the composition of the present invention comprises a mineral sieve of at least one compound selected from the group consisting of zinc oxide, titanium dioxide, or mixtures thereof.

[0120] A list of cited ultraviolet absorbers that may be used in the context of this invention is clearly given by way of non-limiting indication.

[0121] Advantageously, the ultraviolet absorber present in the composition of the present invention accounts for 0.1% to 30% of the total weight of the composition, advantageously between 0.5% and 20%, and even more advantageously between 1% and 15%.

[0122] According to a particular embodiment, the composition of the present invention has a sun protection factor (SPF) greater than or equal to 10, preferably greater than or equal to 20, advantageously greater than or equal to 30, or even more advantageously greater than or equal to 50.

[0123] According to a preferred embodiment, the composition of the present invention has a UV-A / UV-B protection ratio greater than or equal to 1 / 3.

[0124] The sunscreen composition of the present invention contains at least one sunscreen solubilizer.

[0125] The compositions of the present invention may also contain SPF "enhancers," i.e., agents that enhance sun protection factors, and / or light stabilizers, i.e., ingredients used to increase SPF or to light stabilize absorbers; such ingredients are not themselves considered sunscreens. Examples that may be cited include:

[0126] - Butyl octyl salicylate (INCI), a light stabilizer, advantageously constitutes 0.01% to 10% of the total weight of the composition, or even more advantageously 0.1% to 2% of the total weight of the composition;

[0127] - Benzotriazolyl dodecyl p-cresol (INCI), a light stabilizer, advantageously constitutes 0.01% to 10% of the total weight of the composition, or even more advantageously 0.1% to 2% of the total weight of the composition;

[0128] - : Aqua chlorophyll (INCI), a plant molecule that absorbs UV-A, advantageously constitutes 0.5% to 2% of the total weight of the composition, or even more advantageously on the order of 1%;

[0129] - Ethylhexylmethoxypropylene (INCI), light stabilizer, solubilizer and SPF "enhancer", advantageously comprising 1% to 5% of the total weight of the composition;

[0130] - Styrene-acrylate copolymer (INCI: styrene / acrylate copolymer), preferably accounting for 1% to 10% of the total weight of the composition of the present invention;

[0131] - Diethylhexyl eugenyl malonate (INCI), advantageously comprising 1% to 10% of the total weight of the composition;

[0132] - A water-dispersible polyester, corresponding to the INCI name polyester-5 (and) sodium aluminosilicate, advantageously comprising 1% to 10% of the total weight of the composition);

[0133] - An acrylate copolymer with a glass transition temperature of -5°C to -15°C as measured by differential scanning calorimetry, wherein the copolymer advantageously accounts for 1% to 10% of the total weight of the composition.

[0134] According to a particular embodiment, the composition of the present invention further comprises advantageous coloring particles with a blurring effect or a mixture of several particles with a blurring effect. These particles with a blurring effect are also referred to as "soft focus effect particles" or "haze effect particles".

[0135] In the context of this invention, the term "particles with a blurring effect" refers to particles that are advantageously colored and designed to provide greater transparency and a blurring effect to skin tones. In particular, particles with a blurring effect enable compositions containing them to reduce the appearance of fine lines and wrinkles on the skin, especially skin imperfections such as spots, wrinkles, and fine lines, through optical effects.

[0136] Many particles with soft-focus or blurring effects are available on the market. Examples that can be cited are starting materials from the Ronasphere series, which is based on silica and sold by MERCK, and many starting materials sold by JGC-C&C (Coverleaf series, based on sericite or sericite / talc), NIHON KOKEN (ReliefColor Silséem series based on mica / silica), or MIYOSHI KASEI (PC-Bail series based on silica).

[0137] According to yet another embodiment, the starting material KSP-100 of the vinyl polydimethylsiloxane / polymethylsiloxane silsesquioxane crosslinked polymer sold by SHINETSU under the INCI name can be used for the ability to blur effect particles.

[0138] Preferably, the blurring effect particles contained in the composition of the present invention account for 0.5% to 20% of the total weight of the composition, advantageously between 1% and 10%, and even more advantageously between 1% and 5%.

[0139] According to one particular embodiment, the compositions of the present invention may additionally include any fatty substances conventionally used in the cosmetics field. Silicone greases, such as oils, elastic silicone balls, and waxes, may be specifically mentioned; as well as non-silicone fats, such as oils and waxes of plant, mineral, animal, and / or synthetic origin. Oils may be volatile or non-volatile. Hydrocarbons, esters and synthetic esters, fatty alcohols, and fatty acids may also be mentioned.

[0140] According to a particular embodiment, the composition may additionally comprise an aqueous medium, an aqueous alcoholic medium containing an alcohol such as ethanol, or an organic medium containing a common organic solvent such as C1-6 alcohols, particularly ethanol and isopropanol, glycols such as propylene glycol or ketones.

[0141] According to a particular embodiment, the compositions of the present invention further comprise at least one conventional emulsifier selected from amphoteric, anionic, cationic or nonionic emulsifiers, used alone or as a mixture.

[0142] According to a particular embodiment, the compositions of the present invention further comprise commonly used adjuvants in the art of consideration, such as hydrophilic or lipophilic thickeners or gelling agents, hydrophilic or lipophilic additives, active ingredients, particularly cosmetics, preservatives, antioxidants, fragrances, fillers, pigments, odor absorbers, colorants, humectants (glycerin), vitamins, essential fatty acids, fat-soluble polymers, particularly hydrocarbons, opacifiers, stabilizers, chelating agents, conditioning agents, and propellants.

[0143] Obviously, those skilled in the art will carefully select these possible adjuvants or excipients, taking into account their complementary properties and / or their quantities, so that the advantageous properties of the compositions of the present invention are not or will not be substantially altered by the contemplated additives.

[0144] The compositions of the present invention are advantageously formulated to be cosmetically acceptable, i.e., compatible with skin, mucous membranes, hair, and scalp. Preferably, the compositions of the present invention are compositions for application to the skin or for topical use.

[0145] The terms “composition for skin” or “topical use” refer to compositions compatible with application on skin, mucous membranes, hair and / or scalp, preferably human skin.

[0146] The compositions of the present invention can be in any galen formulation suitable for topical application, particularly in the form of aqueous, hydroalcoholic, organic, or oily solutions; suspensions or dispersions in solvents or fats, emulsions, or serums; in the form of vesicle dispersions; in the form of water-in-oil (W / O) emulsions, oil-in-water (O / W) emulsions, or multiple emulsions, such as oil-in-water (W / O / W) emulsions. The consistency of the emulsion can be variable and can be in the form of cream or milk; the compositions of the present invention can also be in the form of ointments, gels or solid bars, pastes or solid anhydrous products, foams, and especially aerosols, as two-phase compositions or practically sprayable compositions.

[0147] The galenal formulation of the composition and its preparation method, as well as the excipients suitable for the compositions of the present invention, can be selected by those skilled in the art based on their general knowledge of the desired type of composition.

[0148] It may be particularly advantageous to formulate the compositions of the present invention in a sprayable manner. For example, this can be done by formulation of a specific emulsion containing a specific combination of excipients.

[0149] According to another aspect, the present invention relates to a cosmetic treatment method comprising applying a composition as defined above to the skin.

[0150] According to another aspect, the present invention relates to a composition, advantageously a cosmetic, comprising at least one glycosylceramide, advantageously a monosaccharide ceramide and / or a polysaccharide ceramide, for the prevention and / or treatment of atopic dermatitis.

[0151] According to a particular embodiment, at least one glycosylceramide, advantageously a monosaccharide ceramide and / or a polysaccharide ceramide, as described above.

[0152] The present invention also relates to a method for treating atopic dermatitis, comprising applying a composition as defined above to the skin.

[0153] According to another aspect, the present invention relates to a composition beneficial to cosmetics, comprising:

[0154] - At least one basic amino acid selected from arginine, lysine, histidine, ornithine, hydroxyproline, and their salts, and

[0155] - At least one glycosylceramide for the prevention and / or treatment of atopic dermatitis.

[0156] According to another particular aspect, the present invention relates to a composition comprising at least one glycosylceramide, advantageously a monosaccharide ceramide and / or a polysaccharide ceramide, preferably in combination with at least one basic amino acid selected from arginine, lysine, histidine, ornithine, hydroxyproline and its salts, for use in...

[0157] - Inducing or increasing the expression of at least one gene encoding a component transmembrane protein of tight junctions, preferably claudin-1; and / or

[0158] - Inducing an increase in the amount of at least one component of a tight junction transmembrane protein, preferably claudin-1; and / or

[0159] - Improve the integrity of tight connections; and / or

[0160] - Strengthens and improves the skin's barrier function.

[0161] According to one particular embodiment, the basic amino acid contained in the composition of the present invention for its use is arginine or one of its salts.

[0162] Advantageously, the compositions according to the invention for use therein contain L-arginine.

[0163] According to a particular embodiment, the composition for use according to the invention comprises at least one glycosylceramide corresponding to monosaccharide ceramide and / or polysaccharide ceramide, advantageously monosaccharide ceramide and / or tetrasaccharide ceramide.

[0164] According to a preferred embodiment, the composition of the present invention for use therein comprises monosaccharide ceramide and glycosaccharide ceramide in the form of tetrasaccharide ceramide.

[0165] According to a particular embodiment, the composition for use according to the invention comprises a monosaccharide ceramide corresponding to glucuronic acid (or gluconic acid) covalently bound to ceramide via a β-glycosidic bond.

[0166] According to a particular embodiment, the polysaccharide ceramide contained in the composition according to the invention for its use corresponds to an oligosaccharide covalently bound to the ceramide via a β-glycosidic bond.

[0167] Advantageously, the polysaccharide ceramide contained in the composition for use according to the invention is a tetrasaccharide ceramide, whose oligosaccharide corresponds to the following sugar in series: glucuronic acid-glucosamine-galactose-mannose (or GlcA-GlcN-Gal-Man).

[0168] The glycosylceramide or multiple glycosylceramides contained in the compositions according to the invention for their use may be of plant or chemical origin, or actually obtained by biotechnology.

[0169] Advantageously, the compositions according to the invention for their use contain at least one biotechnologically derived glycosylceramide.

[0170] Advantageously, all glycosylceramides contained in the compositions of the present invention for their use are of biotechnology origin.

[0171] According to a particular embodiment, at least one basic amino acid, advantageously arginine or a salt thereof, accounts for 0.001% to 2% of the total weight of the composition, advantageously 0.01% to 0.5%.

[0172] According to another specific embodiment, at least one glycosylceramide, advantageously in the form of monosaccharide ceramide and tetrasaccharide ceramide, accounts for 0.0001% to 1% of the total weight of the composition, advantageously 0.001% to 0.1%.

[0173] According to a particular embodiment, the composition used therein according to the invention is as described above (see the first aspect of the invention).

[0174] Advantageously, and for these different therapeutic applications, the compositions of the present invention are in the form of galenol formulations suitable for topical administration.

[0175] One way to demonstrate the preventive and / or therapeutic effect of the compositions according to the invention on atopic dermatitis is, for example, to evaluate the expression of at least one gene encoding a component transmembrane protein of tight junctions, such as claudin-1. Alternatively, it may involve qualitative and / or quantitative analysis of at least one component transmembrane protein of tight junctions (e.g., claudin-1). An example that can be cited is analysis performed by chromatography and / or mass spectrometry, by Western blotting, or practically by immunohistochemical labeling.

[0176] The manner in which the invention is practiced and the advantages therefrom will become apparent from the following exemplary embodiments, which are given in a non-limiting manner with the aid of the accompanying drawings. Attached Figure Description

[0177] Figure 1The effects of arginine (A), glycosylceramide (GC), and combinations thereof (A+GC) on claudin-1 expression in an atopic dermatitis cell model were shown. The "control" condition corresponds to the negative control (no inhibition or T). - ) and positive control (inhibition or T) + The percentage of claudin-1 synthesis induced relative to the positive inhibition control (100%). ** indicates a statistical significance threshold p between 0.001 and 0.01 (highly significant), and *** indicates a statistical significance threshold p < 0.001 (highly significant). Detailed Implementation

[0178] Example 1: Cosmetic composition under the background of the present invention - spray

[0179] The compositions of the present invention are described in Table 1.

[0180]

[0181] Example 2: Cosmetic composition under the background of the present invention—gel

[0182] The compositions of the present invention are described in Table 2.

[0183]

[0184] Example 3: Cosmetic composition within the scope of this invention—O / W emulsion

[0185] The compositions of the present invention are described in Table 3.

[0186]

[0187]

[0188] Example 4: The composition of the present invention affects proteins in an in vitro cell model of atopic dermatitis. claudin-1 The impact of expression

[0189] 1. Materials and Methods

[0190] 1.1 Biological models and cell lines

[0191] Cell lines:

[0192] - Cell type: Normal human epidermal keratinocytes (NHEK; reference: Bioalternatives K34 1), used for 3rd generation - Culture conditions: 37°C, 5% CO2

[0193] Culture medium: SFM (skin keratinocytes), supplemented with epidermal growth factor (or EGF) at a concentration of 0.25 ng / mL, pituitary exudate (PE) at a concentration of 25 µg / mL, and gentamicin at a concentration of 25 µg / mL.

[0194] - Assay medium used in this example: keratinocyte-SFM supplemented with gentamicin at a concentration of 25 µg / mL.

[0195] Cultures of normal human keratinocytes were produced to determine these substances; in short, the protocol is as follows:

[0196] - Keratinocyte differentiation was induced with 0.75 mM calcium for 24 hours;

[0197] - Treat with the compound 1 hour before alarmin induction;

[0198] Treatment with the following alarming agents—histamine, IL-33, and IL-1β—at concentrations of 50 µM, 100 ng / mL, and 100 ng / mL, respectively, was used to induce an atopic dermatitis phenotype characterized by decreased claudin-1 expression.

[0199] Then, claudin-1 immunolabeling was performed.

[0200] 1.2. The active compounds of the compositions of the present invention

[0201] The compounds used alone or in combination in this embodiment are shown in Table 4 below.

[0202]

[0203] 1.3 Cytotoxicity test

[0204] Preliminary cytotoxicity assays were performed on normal human keratinocytes in assay medium containing 0.75 mM CaCl2. These preliminary assays combined the reduction method with MTT tetrazolium (3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide) salt with microscopic morphological observation.

[0205] At the end of the treatment (72 hours of incubation), the cells were incubated in the presence of MTT, which converted into formazan blue crystals, and the activity was directly proportional to that of succinate dehydrogenase (mitochondrial enzyme). After cell dissociation and dissolution of formazan by adding DMSO, the optical density (OD), representing the number of viable cells and their metabolic activity, was measured at 540 nm using a spectrophotometer (VERSAmax, Molecular Devices).

[0206] The results of the MTT survival assay and observation of the cell layer led to the selection of the concentration of the active compound in the compositions of the present invention for determination of the compound of interest in the remainder of the study (see Table 2).

[0207] 1.4 Cultivation and Treatment

[0208] Keratinocytes were then seeded into 96-well plates and cultured in medium for 72 hours, followed by 24 hours in assay medium containing a CaCl2 differentiation inducer (0.75 mM). The medium was then replaced with assay medium containing a CaCl2 inducer (0.75 mM) and with or without (control) the active compound of the present invention (alone or in combination) or a solvent control (0.02% DMSO as determined), followed by 1 hour of pre-incubation. A mixture of alarming agents—histamine, IL-33, and IL-1β—was then added (at concentrations of 50 μM, 100 ng / mL, and 100 ng / mL, respectively), and the cells were incubated for 72 hours. Simultaneously, non-stimulatory / differentiation and non-inhibitory control conditions (assay medium without CaCl2 and alarming agents) and non-inhibitory control conditions (assay medium containing CaCl2 and alarming agents) were generated.

[0209] For each condition, analysis was performed from 30 images (n=30), in addition to the control condition which was generated from 60 images (n=60). The results were evaluated for the first time by considering all quantizations, and then only the results of repeated cultures were evaluated for the second time, i.e., with 3 replicates (n=3), in addition to 6 replicates (n=6) for the control condition.

[0210] 1.5 In situ immunomarking

[0211] After incubation, the culture medium was removed and the cells were washed, fixed, and permeabilized. Cells were then labeled with a primary antibody against claudin-1. This antibody was then visualized using a secondary antibody conjugated with a fluorescent dye (GAM-Alexa 488). Simultaneously, cell nuclei were stained with Hoechst 33258 (bisbenzoimide).

[0212] 1.6 Microscopic observation and image analysis

[0213] Images were acquired using the INCell Analyzer™ 2200 high-resolution imaging system (GE Healthcare; 20x objectives). Ten digital images were acquired for each well.

[0214] The markers were quantified by measuring the fluorescence intensity of the protein relative to the total number of cells identified by bis(benzoimide) staining (using digital data integrated with Developer Toolbox 1.5 software, GE Health Care).

[0215] 1.7 Data Processing

[0216] Use Microsoft Excel® software to transfer and process raw data.

[0217] Between-group comparisons were performed with the aid of two-sided unpaired student t-measures. Statistical analysis can be interpreted if n ≥ 5. However, for n < 5, the calculated data are provided only as indicators.

[0218] Formulas used in this report:

[0219] The standard error (Sem) of the mean represents the difference between the sample mean and the true population mean. Sem is calculated by dividing the standard deviation (Sd) by the square root of the sample size, using the following formula: Sem = Standard Deviation (Sd) / √n;

[0220] - Percentage survival rate is calculated using the following formula: Survival rate (%) = (OD compound / OD control) x 100;

[0221] - The statistical significance thresholds are as follows: ns: > 0.05 (not significant); * = 0.01 to 0.05 (significant); ** = 0.001 to 0.01 (highly significant); *** = < 0.001 (highly significant). Significance is calculated by statistically comparing the differences between the results of each dose of the individual active ingredient and the combination.

[0222] The results are shown in Figure 1.

[0223] 2. Results

[0224] In control conditions without calcium (CaCl2) stimulation / differentiation, the immunomarker of claudin-1 was present as spots in some cells in the cytoplasm and occasionally in the cell membrane.

[0225] As expected, differentiation induction with 0.75 mM CaCl2 increased the expression of the analyzed tight junction protein (claudin-1). This induction was strong and significant, resulting in substantial increases in claudin-1 expression at both the membrane and cytoplasmic levels.

[0226] Keratinocytes stimulated / differentiated with 0.75 mM calcium (CaCl2) were treated with an alarmin mixture (histamine + IL-1 + IL-33 measured at 50 µM + 100 ng / mL + 100 ng / mL) which induced a significant inhibition of claudin-1 expression (the mean of the control was approximately 61.5%).

[0227] The effects of treatment with the active compounds of the present invention, alone or in combination, on claudin-1 expression are shown in the figure. Figure 1 .

[0228] These results show that arginine (A) and glycosylceramide (GC) measured separately (% relative to T+) significantly reversed the inhibitory effect of the alarmin mixture on claudin-1 expression.

[0229] The combination of arginine and glycosylceramide (A+GC) induced claudin-1 expression more strongly than when these compounds were measured alone. The increases were highly significant (***) or extremely significant (**) in all measured concentration combinations, and were not merely complementary in each case, suggesting an unexpected potential synergistic effect of arginine and glycosylceramide in inducing claudin-1 expression, thereby enhancing skin barrier function and preventing and / or treating atopic dermatitis.

[0230] References

[0231] Batista, DIS, Perez, L., Orfali, RL, Zaniboni, MC, Samorano,LP, Pereira, NV, Sotto, MN, Ishizaki, AS, Oliveira, LMS, Sato,MN, et al. (2015). Profile of skin barrier proteins (filaggrin, claudins 1and 4) and Th1 / Th2 / Th17 cytokines in adults with atopic dermatitis. J. Eur.Acad. Dermatol. Venereol. 29: 1091–1095.

[0232] Brandner, J.M., Kief, S., Grund, C., Rendl, M., Houdek, P., Kuhn, C.,Tschachler, E., Franke, W.W., and Moll, I. (2002). Organization and formationof the tight junction system in human epidermis and cultured keratinocytes.Eur. J. Cell Biol. 81: 253–263.

[0233] Cipriani, F., Dondi, A., and Ricci, G. (2014). Recent advances inepidemiology and prevention of atopic eczema. Off. Publ. Eur. Soc. Pediatr.Allergy Immunol. 25: 630–638.

[0234] Gruber, R., Börnchen, C., Rose, K., Daubmann, A., Volksdorf, T.,Wladykowski, E., Vidal-Y-Sy, S., Peters, E.M., Danso, M., Bouwstra, J.A., et al. (2015). Diverse regulation of claudin-1 and claudin-4 in atopicdermatitis. Am. J. Pathol. 185: 2777–2789.

[0235] Halling-Overgaard, A.-S., Kezic, S., Jakasa, I., Engebretsen, K.A.,Maibach, H., and Thyssen, J.P. (2017). Skin absorption through atopicdermatitis skin: a systematic review. Br. J. Dermatol. 177: 84–106.

[0236] Mack, M.R., and Kim, B.S. (2018). The Itch-Scratch Cycle: ANeuroimmune Perspective. Trends Immunol. 39: 980–991.

[0237] Mochizuki, H., Lavery, M.J., Nattkemper, L.A., Albornoz, C., ValdesRodriguez, R., Stull, C., Weaver, L., Hamsher, J., Sanders, K.M., Chan, Y.H., et al. (2019). Impact of acute stress on itch sensation and scratchingbehaviour in patients with atopic dermatitis and healthy controls. Br. J.Dermatol. 180: 821–827.

[0238] Weidinger, S., Beck, L.A., Bieber, T., Kabashima, K., and Irvine,A.D. (2018). Atopic dermatitis. Nat. Rev. Dis. Primer 4: 1.

Claims

1. A composition comprising: - At least one basic amino acid, selected from arginine, lysine, histidine, ornithine, hydroxyproline and their salts; and - At least one glycosylceramide, in the form of a monosaccharide ceramide corresponding to glucuronic acid covalently bound to ceramide, and a tetrasaccharide ceramide corresponding to an oligosaccharide covalently bound to ceramide.

2. The composition according to claim 1, characterized in that, The basic amino acid is arginine or one of its salts.

3. The composition according to claim 1, characterized in that: - The oligosaccharide covalently bound to ceramide is glucuronic acid-glucosamine-galactose-mannose.

4. The composition according to claim 1, characterized in that, The at least one glycosylceramide is obtained by extraction from the membrane of at least one bacterial species.

5. The composition according to claim 1, characterized in that, The at least one basic amino acid accounts for between 0.001% and 2% of the total weight of the composition.

6. The composition according to claim 5, characterized in that, The at least one basic amino acid accounts for between 0.01% and 0.5% of the total weight of the composition.

7. The composition according to claim 1, characterized in that, The at least one glycosylceramide comprises 0.0001% to 1% of the total weight of the composition.

8. The composition according to claim 7, characterized in that, The at least one glycosylceramide comprises 0.001% to 0.1% of the total weight of the composition.

9. The composition according to claim 1, characterized in that, It also includes: - At least one triterpenoid saponin or a derivative thereof, selected from the group consisting of glycyrrhetinic acid, glycyrrhizin, stearyl glycyrrhetinic acid ester and dipotassium diglycyrrhetinate; and / or - At least one nonionic surfactant selected from the group consisting of sorbitol esters and / or sucrose esters.

10. The composition according to claim 9, characterized in that: - At least one triterpenoid saponin or its derivative comprises between 0.0001% and 10% of the total weight of the composition; and / or - At least one nonionic surfactant accounts for between 0.1% and 5% of the total weight of the composition.

11. The composition according to claim 9, characterized in that: - At least one triterpenoid saponin or its derivative comprises between 0.01% and 5% of the total weight of the composition; and / or - At least one nonionic surfactant accounts for between 1% and 3% of the total weight of the composition.

12. The composition according to claim 9 or claim 10, characterized in that, The nonionic surfactant is polysorbate 20 or a sucrose stearate having a hydrophilic-lipophilic balance (HLB) value of at least 16.

13. The composition according to claim 1, characterized in that, It also contains at least one lipid capable of restoring the skin barrier, selected from the following group: - At least one exogenous lipid in the skin; - A mixture of naturally occurring ingredients in the skin, including ceramide-1, ceramide-3, ceramide-6; cholesterol; free fatty acids and phytosphingosine; and - Squalane.

14. The composition according to claim 13, characterized in that, The at least one lipid capable of restoring the skin barrier is selected from the following group: - At least one exogenous lipid in the skin; - A mixture of naturally occurring ingredients in the skin, including ceramide-1, ceramide-3, ceramide-6; cholesterol; free fatty acids and phytosphingosine; and - Squalane.

15. The composition according to claim 14, characterized in that, The at least one exogenous lipid in the skin is a plant oil.

16. The composition according to claim 1, characterized in that, It is a cosmetic composition.

17. The composition according to any one of claims 1, characterized in that, It is a form suitable for local application.

18. Use of the composition according to any one of claims 1 to 17 in the preparation of a medicament for the prevention and / or treatment of atopic dermatitis.

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